Sertraline and Etofenamate: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Sertraline
No brand names on recordEtofenamate
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
You're taking sertraline (an antidepressant) along with etofenamate (an anti-inflammatory pain medicine, an NSAID). On their own, each can make bleeding a little more likely. Sertraline lowers the amount of a chemical called serotonin that your platelets use to help form clots, and NSAIDs can irritate the stomach lining. Put together, they raise your risk of bleeding, especially in the stomach or gut.
Watch for warning signs like black or bloody stools, vomit that looks like coffee grounds, easy bruising, nosebleeds, or unusual stomach pain. The good news is that this is well known and very manageable. Talk with your pharmacist or doctor so they can keep you safe.
Effect: Additive bleeding risk (GI bleeding, intracranial hemorrhage) with concurrent SSRI plus NSAID.
Mechanism: Sertraline depletes platelet serotonin, impairing serotonin-mediated platelet aggregation; etofenamate (NSAID) adds antiplatelet and GI mucosal effects. This is a pharmacodynamic (additive) interaction, not CYP-mediated; neither is a relevant prodrug here.
Evidence: Established. Severity: major. Onset unspecified.
Management:
- Monitor for bleeding, especially GI, in elderly or those with prior ulcer/GI bleed history.
- Consider acetaminophen for pain, or an antidepressant with less serotonin reuptake inhibition.
- Consider gastroprotection (eg, PPI/antiulcer prophylaxis) if both are continued.
What happens
An increased risk of bleeding
Interaction Deep Dive
Exercise caution when NSAIDs and antidepressants, SSRIs among them, are used together, because this combination raises the likelihood of intracranial hemorrhage1 as well as gastrointestinal (GI) bleeding6. Reported bleeding manifestations have ranged from epistaxis, ecchymosis, hematoma, and petechiae to hemorrhages that are life-threatening5. In cases where an SSRI is administered alongside an NSAID, watch the patient carefully for indications of adverse events such as GI bleeds, particularly among the elderly and individuals with a prior history of GI ulcers. Options to consider include alternative approaches to pain control (for example, acetaminophen), reassessing the selected antidepressant (that is, opting for agents that inhibit serotonin reuptake to a lesser degree), or providing prophylaxis using antiulcer medications4.
Why it happens (mechanism)
Depletion of platelet serotonin by SSRI; additive effects on hemostasis
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination is used, but your team will want to keep an eye on your bleeding risk.
Your care team may:
- Watch you more closely for signs of bleeding, especially if you are older or have had stomach ulcers or GI bleeds.
- Suggest a different pain option such as acetaminophen.
- Review whether an antidepressant with less effect on serotonin fits you better.
- Add a stomach-protecting medicine to lower the risk.
Call your pharmacist or doctor right away if you notice black or bloody stools, coffee-ground vomit, unusual bruising, or nosebleeds.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) Taking NSAIDs together with antidepressants, such as tricyclic antidepressants, SSRIs, serotonin-norepinephrine reuptake inhibitors, and MAOIs, was linked to a 60% higher risk of intracranial hemorrhage within 30 days of combined use when compared with using an antidepressant on its own. No meaningful difference in this elevated risk was seen across the various antidepressant drug classes; however, the risk was higher in male patients than in female patients 1.
b) SSRIs raise the likelihood of upper gastrointestinal (GI) bleeding, and this effect is amplified when NSAIDs or low-dose aspirin are used at the same time. Hospitalizations for upper GI bleeding were reviewed among 26,005 people taking antidepressant drugs and were compared with the number of hospitalizations among patients who were not prescribed antidepressants. The number of upper GI bleeding events was 3.6 times higher than anticipated. Using an SSRI together with NSAIDs or low-dose aspirin raised the risk to 12.2 and 5.2 times, respectively. These results show a heightened risk of upper GI bleeding while SSRIs are being used. Concurrent use of SSRIs with NSAIDs or low-dose aspirin raised the risk even more 5.
c) Two metaanalyses examining cases of upper GI bleeding related to SSRIs, NSAIDs, and their combination found that SSRIs raised the risk by 1.73 6 to 2.36 times 7, NSAIDs by 2.55 times 6, and the combination of SSRIs and NSAIDs by 4.02 6 to 6.33 times 7.
d) The release of serotonin from platelets plays an important role in preserving hemostasis. Case-control and cohort studies have demonstrated that using SSRIs and NSAIDs together has been associated with a greater risk of bleeding 8.
Common questions
Can I take Sertraline and Etofenamate together?
Taking sertraline with the NSAID etofenamate raises your risk of bleeding, especially in the stomach and gut, so watch for bleeding signs and ask your care team about safer pain options or stomach protection. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sertraline and Etofenamate interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Sertraline and Etofenamate interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination is used, but your team will want to keep an eye on your bleeding risk. Your care team may: Watch you more closely for signs of bleeding, especially if you are older or have had stomach ulcers or GI bleeds. Suggest a different pain option such as acetaminophen. Review whether an antidepressant with le… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Sertraline or Etofenamate need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (8)
- Shin JY, Park MJ, Lee SH, et al: Risk of intracranial haemorrhage in antidepressant users with concurrent use of non-steroidal anti-inflammatory drugs: nationwide propensity score matched study. BMJ 2015; 351:h3517. PubMed
- Product Information: VIMOVO(TM) delayed release oral tablets, naproxen and esomeprazole magnesium delayed release oral tablets. AstraZeneca LPW, Wilmington, DE, 2010. DailyMed
- Product Information: SPRIX(TM) nasal spray, ketorolac tromethamine nasal spray. Roxro Pharma, Inc, Menlo Park, CA, 2009. DailyMed
- Mort JR, Aparasu RR, & Baer RK: Interaction between selective serotonin reuptake inhibitors and nonsteroidal antiinflammatory drugs: review of the literature. Pharmacotherapy 2006; 26(9):1307-1313. PubMed
- Dalton S, Johansen C, Mellemkjoer L, et al: Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding. Arch Intern Med 2003; 163:59-64. DOI
- Oka Y, Okamoto K, Kawashita N, et al: Meta-analysis of the risk of upper gastrointestinal hemorrhage with combination therapy of selective serotonin reuptake inhibitors and non-steroidal anti-inflammatory drugs. Biol Pharm Bull 2014; 37(6):947-953. PubMed
- Loke YK, Trivedi AN, & Singh S: Meta-analysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 2008; 27(1):31-40. PubMed
- Product Information: CELEXA(R) oral tablets, citalopram oral tablets. Allergan USA Inc (per FDA), Madison, NJ, 2023. DailyMed
Keep reading about Sertraline
Keep reading about Etofenamate
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